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Therapeutic Advances in Urology 2022Bladder pain syndrome/interstitial cystitis (BPS/IC) is a persistent pain perceived in the urinary bladder region, accompanied by at least one symptom, such as pain...
BACKGROUND
Bladder pain syndrome/interstitial cystitis (BPS/IC) is a persistent pain perceived in the urinary bladder region, accompanied by at least one symptom, such as pain worsening with bladder filling and daytime or nighttime urinary frequency without any proven infection or obvious pathology. The aim of this study is to evaluate the efficacy and safety of pentosan polysulfate (PPS) in patients with BPS/IC.
METHODS
Systematic search was performed by PRISMA checklist. Electronic databases, including PubMed and Cochrane library, were checked until 2021 using keywords: 'pentosan polysulfate', 'pain syndrome', 'interstitial cystitis', and bibliography of relevant papers was checked.
INCLUSION CRITERIA
Patients with confirmed diagnosis of BPS/IC and cystoscopy criteria - Hunner's lesions. Exclusion criteria included hypersensitivity, pregnancy, lactation, and oral therapy for BPS/IC in the period of 1 month before the study and abstracts or unpublished papers.
RESULTS
In total, 13 clinical trials were included in systematic review and 7 were included in meta-analysis. Studies evaluated the effectiveness and safety of oral PPS placebo or other treatment options. In the first meta-analysis, three studies compared oral PPS with placebo: [relative risk (RR) = 2.07, 95% confidence interval (CI): 1.37-3.13, = 0.0006]. The second meta-analysis of two studies compared oral PPS with another treatment options (intravesical liposome and CyA): (RR = 0.44, 95% CI: 0.10-1.93, = 0.28). The third meta-analysis of two studies included intravesical regimen of PPS compared with intravesical placebo: (RR = 1.09, 95% CI: 0.54-2.22, = 0.80). The majority of studies do not report any particular serious side effects.
CONCLUSION
PPS treatment has a statistically significant effect over placebo on the subjective improvement of patients with BPS/IC. There was no difference between PPS and other treatment options. Intravesical regimen of PPS had no significant impact on response rates. None of included studies reported severe side effects after intervention.
PubMed: 35677571
DOI: 10.1177/17562872221102809 -
Scientific Reports May 2024In this population-based cohort study, we investigated screening practices for maculopathy and incidences of specific macular/retinal conditions in pentosan polysulfate...
In this population-based cohort study, we investigated screening practices for maculopathy and incidences of specific macular/retinal conditions in pentosan polysulfate (PPS) users and assessed the relationship between these outcomes and drug exposure levels. Using a health claims database that covers approximately 50 million Koreans, we identified 138,593 individuals who were prescribed PPS between 2010 and 2021. For the 133,762 PPS users who initiated therapy between 2012 and 2021, the cumulative PPS dose for each participant was evaluated, and based on their cumulative PPS dose, patients were categorized into the high-risk (≥ 500 g), low-risk (50-500 g), and minimal exposure (< 50 g) groups. We analyzed the performance and methods of these examination methods used between 2018 and 2021 and compared them among cumulative dose groups to determine whether high-risk users underwent maculopathy screening more frequently or appropriately. We assessed the cumulative incidence of overall macular degeneration and maculopathy excluding common macular diseases following PPS therapy initiation. Most PPS users (99.7%) received a cumulative PPS dose < 500 g and the high- and low-risk groups comprised 445 (0.3%) and 22,185 (16.6%) patients, respectively. During the study period, monitoring examinations were conducted in 52.6% and 49.4% of high- and low-risk patients, respectively, revealing no significant difference between the two groups (P = 0.156). No significant differences were observed in the annual percentages of patients receiving ophthalmic examinations between the high- and low-risk groups (all P > 0.05). The cumulative incidences of overall macular degeneration and maculopathy excluding common macular diseases in high-risk users were 19.3% and 9.0%, respectively, which were significantly different from those of low-risk users (both P < 0.001). Multivariate Cox regression analysis revealed significantly higher risks of maculopathy excluding common macular diseases in the low- (Hazard ratio [HR] of 1.55 [95% CI 1.13-2.12]) and high-risk groups (HR of 1.66 [95% CI 1.22-2.27]) compared to the minimal exposure group. Our findings suggest a need for increased emphasis on PPS maculopathy screening in high-risk patients, highlighting raising awareness regarding exposure-dependent risks and the establishment of screening guidelines.
Topics: Humans; Pentosan Sulfuric Polyester; Male; Female; Middle Aged; Macular Degeneration; Risk Assessment; Aged; Adult; Incidence; Republic of Korea; Mass Screening; Cohort Studies
PubMed: 38760453
DOI: 10.1038/s41598-024-62041-y -
Osteoarthritis and Cartilage Open Jun 2023To evaluate the efficacy and safety of pentosan polysulfate sodium (PPS, Elmiron®) for dyslipidaemia and knee osteoarthritis (OA) related symptoms. (Clinical Trial)
Clinical Trial
OBJECTIVE
To evaluate the efficacy and safety of pentosan polysulfate sodium (PPS, Elmiron®) for dyslipidaemia and knee osteoarthritis (OA) related symptoms.
METHOD
This was a single-arm, open-label, prospective, non-randomised pilot study. People with painful knee OA and a history of primary hypercholesterolemia were included. PPS was taken orally in a dosage of 10 mg/kg once every 4 days for 5 weeks for two cycles. There was 5 weeks of no medication between the cycles. The main outcomes included the change in lipidemia levels, the change in knee OA-related symptoms assessed by pain numerical rating scale (NRS) and Knee Osteoarthritis Outcome Score (KOOS), and knee MRI semi-quantitative score. The changes were analysed using paired t-tests.
RESULTS
38 participants were included, with a mean age of 62.2 years. We found a statistically significant decrease in total cholesterol (from 6.23 ± 0.74 to 5.95 ± 0.77 mmol/L; = 0.01) and low-density lipoprotein (from 4.03 ± 0.61 to 3.82 ± 0.61 mmol/L; = 0.009) from baseline to week 16. Knee pain NRS was significantly reduced at weeks 6, 16 and 26 from 6.39 ± 1.33 to 4.18 ± 1.99, 3.63 ± 2.28 and 4.38 ± 2.55, respectively ( < 0.001). However, there was no significant difference in terms of the primary outcome of triglyceride levels before and after treatment. The most common AEs were positive faecal occult blood tests, followed by headache and diarrhoea.
CONCLUSION
The findings suggest that PPS has promising effects on improving dyslipidaemia and symptomatic pain relief in people with knee OA.
PubMed: 36879559
DOI: 10.1016/j.ocarto.2023.100343 -
PloS One 2022Hepcidin which is the crucial regulator of iron homeostasis, produced in the liver in response to anemia, hypoxia, or inflammation. Recent studies have suggested that...
Hepcidin which is the crucial regulator of iron homeostasis, produced in the liver in response to anemia, hypoxia, or inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis by inhibiting osteoblast function and promoting osteoclastogenesis. Pentosan polysulfate (PPS) is a heparin analogue and promising novel therapeutic for osteoarthritis (OA). This study was undertaken to determine whether PPS inhibits hepcidin-facilitated osteoclast (OC) differentiation and iron overload. Canine (n = 3) bone marrow mononuclear cells were differentiated to OC by macrophage colony-stimulating factor and receptor-activator of nuclear factor kappaB ligand with the treatment of hepcidin1 (200, 400, 800, 1200 nmol/L) and PPS (1, 5, 10, 20, 40 μg/mL). Differentiation and function of OC were accessed using tartrate-resistant acid phosphate staining and bone resorption assay while monitoring ferroportin1 (FPN1) and iron concentration by immunocytochemistry. Gene expression of OC for cathepsin K (CTK), matrix metallopeptidase-9, nuclear factor of activated-T-cells cytoplasmic 1 and FPN1 was examined. Hepcidin1 showed significant enhancement of OC number at 800 nmol/L (p<0.01). PPS impeded hepcidin-facilitated OC at 1, 5 and 10 μg/mL and reduction of resorption pits at 5 and 10 μg/mL (p< 0.01). All OC specific genes were downregulated with PPS, specifically in significant manner with CTK at higher concentrations. However, heparin induced FPN1 internalization and degradation was inhibited at higher concentrations of PPS while restoring iron-releasing capability of OC. We demonstrate for the first time that PPS is a novel-inhibitor of hepcidin-facilitated OC formation/function which might be beneficial for treatment of OA and osteoporosis.
Topics: Animals; Bone Marrow; Bone Resorption; Cell Differentiation; Dogs; Heparin; Hepcidins; Iron; Osteoarthritis; Osteoclasts; Osteoporosis; Pentosan Sulfuric Polyester; RANK Ligand
PubMed: 35299233
DOI: 10.1371/journal.pone.0265596 -
Thrombosis and Haemostasis Jun 2022Two years since the outbreak of the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, there remain few clinically effective drugs...
Two years since the outbreak of the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, there remain few clinically effective drugs to complement vaccines. One is the anticoagulant, heparin, which in 2004 was found able to inhibit invasion of SARS-CoV (CoV-1) and which has been employed during the current pandemic to prevent thromboembolic complications and moderate potentially damaging inflammation. Heparin has also been shown experimentally to inhibit SARS-CoV-2 attachment and infection in susceptible cells. At high therapeutic doses however, heparin increases the risk of bleeding and prolonged use can cause heparin-induced thrombocytopenia, a serious side effect. One alternative, with structural similarities to heparin, is the plant-derived, semi-synthetic polysaccharide, pentosan polysulfate (PPS). PPS is an established drug for the oral treatment of interstitial cystitis, is well-tolerated, and exhibits weaker anticoagulant effects than heparin. In an established Vero cell model, PPS and its fractions of varying molecular weights inhibited invasion by SARS-CoV-2. Intact PPS and its size-defined fractions were characterized by molecular weight distribution and chemical structure using nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry, then employed to explore the structural basis of interactions with SARS-CoV-2 spike protein receptor-binding domain (S1 RBD) and the inhibition of Vero cell invasion. PPS was as effective as unfractionated heparin, but more effective in inhibiting cell infection than low-molecular-weight heparin (on a weight/volume basis). Isothermal titration calorimetry and viral plaque-forming assays demonstrated size-dependent binding to S1 RBD and inhibition of Vero cell invasion, suggesting the potential application of PPS as a novel inhibitor of SARS-CoV-2 infection.
Topics: Animals; Anticoagulants; Chlorocebus aethiops; Heparin; Pentosan Sulfuric Polyester; Protein Binding; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Vero Cells; Virus Attachment
PubMed: 35322395
DOI: 10.1055/a-1807-0168 -
Stem Cells and Development Aug 2022This review highlights the attributes of pentosan polysulfate (PPS) in the promotion of intervertebral disc (IVD) repair processes. PPS has been classified as a... (Review)
Review
Pentosan Polysulfate, a Semisynthetic Heparinoid Disease-Modifying Osteoarthritic Drug with Roles in Intervertebral Disc Repair Biology Emulating the Stem Cell Instructive and Tissue Reparative Properties of Heparan Sulfate.
This review highlights the attributes of pentosan polysulfate (PPS) in the promotion of intervertebral disc (IVD) repair processes. PPS has been classified as a disease-modifying osteoarthritic drug (DMOAD) and many studies have demonstrated its positive attributes in the countering of degenerative changes occurring in cartilaginous tissues during the development of osteoarthritis (OA). Degenerative changes in the IVD also involve inflammatory cytokines, degradative proteases, and cell signaling pathways similar to those operative in the development of OA in articular cartilage. PPS acts as a heparan sulfate (HS) mimetic to effect its beneficial effects in cartilage. The IVD contains small cell membrane HS proteoglycans (HSPGs) such as syndecan, and glypican and a large multifunctional HS/chondroitin sulfate (CS) hybrid proteoglycan (HSPG2/perlecan), that have important matrix-stabilizing properties and sequester, control, and present growth factors from the FGF, VEGF, PDGF, and BMP families to cellular receptors to promote cell proliferation, differentiation, and matrix synthesis. HSPG2 also has chondrogenic properties and stimulates the synthesis of extracellular matrix (ECM) components and expansion of cartilaginous rudiments, and has roles in matrix stabilization and repair. Perlecan is a perinuclear and nuclear proteoglycan (PG) in IVD cells with roles in chromatin organization and control of transcription factor activity, immunolocalizes to stem cell niches in cartilage, promotes escape of stem cells from quiescent recycling, differentiation and attainment of pluripotency and migratory properties. These participate in tissue development and morphogenesis, ECM remodeling and repair. PPS also localizes in the nucleus of stromal stem cells, promotes development of chondroprogenitor cell lineages, ECM synthesis and repair and discal repair by resident disc cells. The availability of recombinant perlecan and PPS offers new opportunities in repair biology. These multifunctional agents offer welcome new developments in repair strategies for the IVD.
Topics: Cartilage, Articular; Extracellular Matrix Proteins; Heparan Sulfate Proteoglycans; Heparinoids; Heparitin Sulfate; Humans; Intervertebral Disc; Pentosan Sulfuric Polyester; Stem Cells
PubMed: 35102748
DOI: 10.1089/scd.2022.0007 -
Retina (Philadelphia, Pa.) Jul 2021To investigate patient-reported visual function among individuals taking pentosan polysulfate (PPS) for interstitial cystitis.
PURPOSE
To investigate patient-reported visual function among individuals taking pentosan polysulfate (PPS) for interstitial cystitis.
METHODS
A 27-item online survey was distributed to an international mailing list of individuals with interstitial cystitis in November 2018. Demographic characteristics, PPS exposure history, subjective visual function, and previous macular diagnoses were queried. The impact of PPS use, grouped by tertile of cumulative exposure, on visual function and macular diagnoses was assessed with multivariate logistic regression.
RESULTS
The survey was completed by 912 respondents. Eight hundred and sixty-one (96.4%) were women, and the median age was 55 [interquartile range (IQR), 45-64 years]. Among PPS users, the median exposure was 547.5 g (IQR, 219-1,314 g). Respondents in the highest PPS exposure tertile were more likely to report difficulty with reading small print [adjusted odds ratio 2.29, 95% confidence interval (CI) 1.15-4.57] and to have a diagnosis of macular degeneration and/or pigmentary maculopathy (adjusted odds ratio 2.41, 95% CI 1.44-4.03) than unexposed respondents.
CONCLUSION
In this large sample of individuals with interstitial cystitis, those in the highest PPS exposure category were more likely to have difficulties reading small print and to report a previous diagnosis of macular disease. Further study of objective measures of visual function in PPS users is warranted.
Topics: Anticoagulants; Cystitis, Interstitial; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pentosan Sulfuric Polyester; Retinal Diseases; Retinal Pigment Epithelium; Retrospective Studies; Surveys and Questionnaires
PubMed: 33332810
DOI: 10.1097/IAE.0000000000003078 -
Urology Jan 2021To conduct a review of current literature to assess whether an association exists between Pentosan Polysulfate Sodium and the development of macular disease, as it is...
OBJECTIVE
To conduct a review of current literature to assess whether an association exists between Pentosan Polysulfate Sodium and the development of macular disease, as it is the only oral medication approved by the Food and Drug Administration for the management of interstitial cystitis.
MATERIALS AND METHODS
A systematic review was conducted by the authors separately, with review methods established prior to the conduct of the review. Databases searched included PubMed, Ovid, Medline, EBSCO, and Google Scholar. A search was conducted for the terms "Pentosan Polysulfate Maculopathy," "Pentosan Polysulfate Retinopathy," and "Interstitial Cystitis Maculopathy." All papers reporting on primary data were included. There were no study sponsors.
RESULTS
A total of 14 papers reporting on primary data were identified. Most papers reported on the development of macular disease in the setting of chronic pentosan polysulfate sodium exposure. No randomized controlled trials have been performed to date and data was insufficient to perform a meta-analysis. Nevertheless, patients with interstitial cystitis were more likely to receive a diagnosis of maculopathy after several years of the medication use.
CONCLUSION
Although the nature of the published studies renders them prone to confounders, currently available data suggest an increased risk for developing maculopathy after years of pentosan polysulfate sodium use. In light of this, and the marginal effectiveness of the medication for the average individual, we suggest that education be provided as to the possible association and that regular ophthalmic evaluation be recommended for patients who are continued on chronic Pentosan Polysulfate Sodium.
Topics: Cystitis, Interstitial; Humans; Macular Degeneration; Pentosan Sulfuric Polyester; Prevalence; Urologists
PubMed: 33045286
DOI: 10.1016/j.urology.2020.08.072 -
Expert Opinion on Pharmacotherapy Aug 2019
PubMed: 31070933
DOI: 10.1080/14656566.2019.1615056 -
Central European Journal of Urology 2021Bladder pain syndrome/interstitial cystitis (BPS/IC) is a condition that is characterized by urgency, frequency and/or pelvic pain. The disease occurs mainly in women....
Safety and efficacy of pentosan polysulfate in patients with bladder pain syndrome/interstitial cystitis: a multicenter, double-blind, placebo-controlled, randomized study.
INTRODUCTION
Bladder pain syndrome/interstitial cystitis (BPS/IC) is a condition that is characterized by urgency, frequency and/or pelvic pain. The disease occurs mainly in women. BPS/IC can be severe enough to have a significant impact on patients' quality of life, but it can also be associated with moderate symptoms that are equally debilitating.The aim of this article was to evaluate the possibility of the use of pentosan polysulfate sodium in patients in the complex treatment of BPS/IC.
MATERIAL AND METHODS
A multicenter, double-blind, placebo-controlled, randomized study was conducted in parallel groups in 7 Russian medical centers.
RESULTS
Efficacy and safety have been established as the main criteria. A total of 93 patients were screened. Statistical analysis was performed. It has been shown that pentosan therapy is more effective than in the placebo. Average change in the number of points on the scale O'Leary-Santa Interstitial Cystitis Symptom Index compared to baseline data in the pentosan group 4.93 ±3, 03, in the placebo group 1.66 ±3.19 (p = 0.014), and the adverse events and safety of pentosan are comparable to the placebo group.
CONCLUSIONS
Oral glycosaminoglycan (pentosan polusulfate sodium) is an effective and safe drug and should be included in the complex treatment of patients with bladder pain syndrome/interstitial cystitis.
PubMed: 34336239
DOI: 10.5173/ceju.2021.0340.R1